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Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis (BISCIT) (BISCIT)

Primary Purpose

Secondary Sclerosing Cholangitis

Status
Terminated
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Endoscopic retrograde cholangiography (ERC)
Sponsored by
Hannover Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Secondary Sclerosing Cholangitis focused on measuring biliary intervention, endoscopic therapy, endoscopic retrograde cholangiography

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients have to fulfill all of the following inclusion criteria to be eligible for participation in this study:

  1. Men, women*, inter/divers, age ≥18 and ≤ 80 years (conscious or unconscious patients may be included)
  2. Signed written informed consent obtained by patient or legal representative in case of unconscious patient
  3. Willingness to comply with treatment and follow-up procedures
  4. Suspected SSC-CIP = episode of critical illness and intensive care unit treatment > 3 days within last 12 months
  5. SSC-CIP is confirmed by ERC, (if the first ERC is performed at baseline, the patient may be considered as screening failure if the diagnosis is not confirmed)
  6. Elevation of bilirubin ≥ 2.5 upper limit of normal (ULN) at Screening
  7. Elevation of alkaline phosphatase (AP) or gamma-glutamyl-transferase (GGT) > 2.5 ULN or elevation of both at Screening

  8. *Women without childbearing potential defined as follows:

    • at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or
    • hysterectomy or uterine agenesis or
    • ≥ 50 years and in postmenopausal state > 1 year or

    • < 50 years and in postmenopausal state > 1 year with serum Follicle Stimulating Hormone (FSH) > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening or

      *Women of childbearing potential:

    • who are practicing sexual abstinence (periodic abstinence and withdrawal are not acceptable) or
    • who have sexual relationships with female partners only and/or with sterile male partners or
    • who are sexually active with fertile male partner, have a negative pregnancy test during screening and agree to use reliable methods of contraception (failure rate of < 1% per year) from the time of screening until end of the clinical trial.

Exclusion Criteria:

  1. Patient is too unstable to undergo ERC
  2. Inclusion in any other intervention trial within the last 30 days
  3. Pregnancy or lactation period

Sites / Locations

  • Hannover Medical School

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

interventional

control

Arm Description

The intervention group undergoes scheduled invasive evaluation of the biliary tract with endoscopic retrograde cholangiography (ERC) with biliary interventions (i.e. therapeutic ERC) every 8 weeks for 6 months.

The control group receives non-interventional standard of care.

Outcomes

Primary Outcome Measures

occurrence of death
The primary endpoint is the failure rate defined as a composite endpoint consisting of occurrence of death or necessity of liver transplantation or occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
necessity of liver transplantation
The primary endpoint is the failure rate defined as a composite endpoint consisting of occurrence of death or necessity of liver transplantation or occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
The primary endpoint is the failure rate defined as a composite endpoint consisting of occurrence of death or necessity of liver transplantation or occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.

Secondary Outcome Measures

Laboratory parameters (bilirubin in µmol/L) as change from baseline
Laboratory parameters (alkaline phosphatase in U/L) as change from baseline
Laboratory parameters (gamma-glutamyltransferase) as change from baseline
Laboratory parameters (aspartate aminotransferase in U/L) as change from baseline
Laboratory parameters (alanine aminotransferase in U/L) as change from baseline
Laboratory parameters (lactate dehydrogenase in U/L) as change from baseline
Laboratory parameters (glutamate dehydrogenase in U/L) as change from baseline
Laboratory parameters (creatinine in µmol/L) as change from baseline
Laboratory parameters (c-reactive protein in mg/L) as change from baseline
Laboratory parameters (cholinesterase in kU/L) as change from baseline
To analyze course of liver function (Model for endstage liver disease score as changes from baseline)
Model for End-Stage Liver Disease (MELD) score 0-40 points with higher values indicating increasing impairment of liver function
Occurrence of unplanned Intensive care unit (ICU) admissions (necessity and days free of: intensive care unit care, invasive ventilation, renal replacement therapy, vasopressors within 6 months)
To analyze the need for anti-infective therapy (antibiotic treatment) in the different study arms
Necessity of treatment with anti-infective medication (= treament with antibiotic oral or intravenously for acute cholangitis) (yes/no)
Occurrence of unplanned hospital admissions (necessity and days free of hospital care within 6 months)

Full Information

First Posted
May 3, 2022
Last Updated
October 9, 2023
Sponsor
Hannover Medical School
Collaborators
German Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05396755
Brief Title
Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis (BISCIT)
Acronym
BISCIT
Official Title
Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis - a Multicenter, Randomized Controlled, Parallel Group Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Study was stopped due to insufficient recruitment.
Study Start Date
November 14, 2022 (Actual)
Primary Completion Date
September 14, 2023 (Actual)
Study Completion Date
September 14, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hannover Medical School
Collaborators
German Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized, open-label, controlled, parallel group, multicenter clinical trial. Patients with confirmed secondary sclerosing cholangitis (SSC-CIP) will be randomized either in the intervention group undergoing scheduled invasive evaluation of the biliary tract or in the control group treated with non-interventional standard of care to demonstrate that programmed endoscopic therapy compared to a conservative strategy reduces the occurrence of treatment failures.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Sclerosing Cholangitis
Keywords
biliary intervention, endoscopic therapy, endoscopic retrograde cholangiography

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
randomized, open-label, controlled, parallel group, multicenter
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
interventional
Arm Type
Experimental
Arm Description
The intervention group undergoes scheduled invasive evaluation of the biliary tract with endoscopic retrograde cholangiography (ERC) with biliary interventions (i.e. therapeutic ERC) every 8 weeks for 6 months.
Arm Title
control
Arm Type
No Intervention
Arm Description
The control group receives non-interventional standard of care.
Intervention Type
Procedure
Intervention Name(s)
Endoscopic retrograde cholangiography (ERC)
Intervention Description
invasive evaluation of the biliary tract with ERC and endoscopic interventions every 8 weeks until 6 months (24 weeks)
Primary Outcome Measure Information:
Title
occurrence of death
Description
The primary endpoint is the failure rate defined as a composite endpoint consisting of occurrence of death or necessity of liver transplantation or occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
Time Frame
up to week 48
Title
necessity of liver transplantation
Description
The primary endpoint is the failure rate defined as a composite endpoint consisting of occurrence of death or necessity of liver transplantation or occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
Time Frame
up to week 48
Title
occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
Description
The primary endpoint is the failure rate defined as a composite endpoint consisting of occurrence of death or necessity of liver transplantation or occurrence of cholangiosepsis (defined by SEPSIS-3 criteria and diagnosis of acute cholangitis according to the Tokyo Guidelines), whatever occurs first.
Time Frame
up to week 48
Secondary Outcome Measure Information:
Title
Laboratory parameters (bilirubin in µmol/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (alkaline phosphatase in U/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (gamma-glutamyltransferase) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (aspartate aminotransferase in U/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (alanine aminotransferase in U/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (lactate dehydrogenase in U/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (glutamate dehydrogenase in U/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (creatinine in µmol/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (c-reactive protein in mg/L) as change from baseline
Time Frame
week 24
Title
Laboratory parameters (cholinesterase in kU/L) as change from baseline
Time Frame
week 24
Title
To analyze course of liver function (Model for endstage liver disease score as changes from baseline)
Description
Model for End-Stage Liver Disease (MELD) score 0-40 points with higher values indicating increasing impairment of liver function
Time Frame
week 24
Title
Occurrence of unplanned Intensive care unit (ICU) admissions (necessity and days free of: intensive care unit care, invasive ventilation, renal replacement therapy, vasopressors within 6 months)
Time Frame
week 24
Title
To analyze the need for anti-infective therapy (antibiotic treatment) in the different study arms
Description
Necessity of treatment with anti-infective medication (= treament with antibiotic oral or intravenously for acute cholangitis) (yes/no)
Time Frame
week 24
Title
Occurrence of unplanned hospital admissions (necessity and days free of hospital care within 6 months)
Time Frame
week 24
Other Pre-specified Outcome Measures:
Title
Changes in specific signatures in biliary microbiome
Time Frame
day1, week 8, week 16, week 24
Title
To analyze the extent of biliary tract damage at magnetic resonance cholangiopancreatography (MRCP) in the different study arms.
Description
Extent of bile duct damage at 6-months MRCP compared to baseline as determined by central radiology reading
Time Frame
week 24
Title
Occurrence of infections: cholangitis, cholecystitis
Time Frame
up to week 48
Title
Occurrence of ERC-related complications: bleeding, perforation, pancreatitis, cholangitis,
Time Frame
day1, week 8, week 16, week 24
Title
occurrence of serious adverse events
Description
population
Time Frame
day1, week 8, week 16, week 24, week 32, week 40, week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients have to fulfill all of the following inclusion criteria to be eligible for participation in this study: Men, women*, inter/divers, age ≥18 and ≤ 80 years (conscious or unconscious patients may be included) Signed written informed consent obtained by patient or legal representative in case of unconscious patient Willingness to comply with treatment and follow-up procedures Suspected SSC-CIP = episode of critical illness and intensive care unit treatment > 3 days within last 12 months SSC-CIP is confirmed by ERC, (if the first ERC is performed at baseline, the patient may be considered as screening failure if the diagnosis is not confirmed) Elevation of bilirubin ≥ 2.5 upper limit of normal (ULN) at Screening Elevation of alkaline phosphatase (AP) or gamma-glutamyl-transferase (GGT) > 2.5 ULN or elevation of both at Screening *Women without childbearing potential defined as follows: at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or hysterectomy or uterine agenesis or ≥ 50 years and in postmenopausal state > 1 year or < 50 years and in postmenopausal state > 1 year with serum Follicle Stimulating Hormone (FSH) > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening or *Women of childbearing potential: who are practicing sexual abstinence (periodic abstinence and withdrawal are not acceptable) or who have sexual relationships with female partners only and/or with sterile male partners or who are sexually active with fertile male partner, have a negative pregnancy test during screening and agree to use reliable methods of contraception (failure rate of < 1% per year) from the time of screening until end of the clinical trial. Exclusion Criteria: Patient is too unstable to undergo ERC Inclusion in any other intervention trial within the last 30 days Pregnancy or lactation period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans H. Wedemeyer, Prof.
Organizational Affiliation
Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hannover Medical School
City
Hannover
State/Province
Lower Saxony
ZIP/Postal Code
30625
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

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Biliary Interventions in Critically Ill Patients With Secondary Sclerosing Cholangitis (BISCIT)

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